Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

5'-modified bicyclic nucleic acid analogs

A kind of technology of bicyclic nucleosides and compounds, applied in the field of oligomers or compositions

Active Publication Date: 2009-07-22
IONIS PHARMA INC
View PDF144 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Thus, there remains a long-felt unmet need for agents that specifically modulate gene expression through an antisense mechanism

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 5'-modified bicyclic nucleic acid analogs
  • 5'-modified bicyclic nucleic acid analogs
  • 5'-modified bicyclic nucleic acid analogs

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0053] Representative U.S. patents that teach the preparation of representative motifs include, but are not limited to: 5,013,830, 5,149,797, 5,220,007, 5,256,775, 5,366,878, 5,403,711, 5,491,133, 5,565,350, 5,623,065, 5,652,355, 5,652,3706, some of which; This application is commonly owned, each of which is incorporated herein by reference in its entirety. Motif filed on June 2, 2005 and published on December 22, 2005 as WO 2005 / 121371 International Application PCT / US2005 / 019219 and filed on June 2, 2005 and published on December 22, 2005 It is also disclosed in PCT / US2005 / 019220 as WO 2005 / 121372, each of which is incorporated herein by reference in its entirety.

[0054] The terms "stable compound" and "stable structure" refer to a compound that is sufficiently robust to be isolated to a useful degree of purity from a reaction mixture and formulated as an effective therapeutic agent. Only stable compounds are concerned here.

[0055] Selected substituent groups within the c...

Embodiment 1

[0132] (1R, 3R, 4R, 7S)-7-[2-cyanoethoxy(diisopropylamino)phosphineoxy]-1-[1-(S)-(4,4'-dimethoxy Preparation of Trityl)oxy-ethyl]-3-(uracil-1-yl)-2,5-dioxa-bicyclo[2.2.1]heptane (19a)

[0133]

[0134] Route 1(a) TBSCl, Et 3 N,DMAP,CH 2 Cl 2 , room temperature, 16h(b) oxalyl chloride, DMSO, Et 3 N, CH 2 Cl 2 , -78°C to room temperature (c) MeMgBr, CeCl 3 , THF, -78°C (d) isobutyryl chloride, Et 3 N,DMAP,CH 2 Cl 2 , room temperature, 16h(e) 70% HF / pyridine, room temperature, 16h(f) methanesulfonyl chloride, Et 3 N,DMAP,CH 2 Cl 2 (g) AcOH, Ac 2 O, concentrated H 2 SO 4 (h) Uracil, BSA, TMSOTf, CH 3 CN, reflux, 2h (i) NaOH, water, dioxane (j) isobutyric anhydride, DMAP, pyridine (k) Pd / C, H 2 Balloon (1) TBSCl, Imidazole, DMF(m)K 2 CO 3 , MeOH(n)DMTCl, 2,6-lutidine, pyridine, 45℃(o)Et 3 N.3HF, Et 3 N,THF(p)(iPr 2 N) 2 POCH 2 CH 2 CN, tetrazole, NMI, DMF.

[0135] A) Preparation of Compound 4

[0136] A solution of tert-butyldimethylsilyl chloride (6.2...

Embodiment 2

[0170] (1R, 3R, 4R, 7S)-7-[2-cyanoethoxy(diisopropylamino)phosphineoxy]-1-[1-(R)-(4,4'-dimethoxy Preparation of Trityl)oxy-ethyl]-3-(uracil-1-yl)-2,5-dioxa-bicyclo[2.2.1]heptane, compound 19b (Scheme 1)

[0171] A) Preparation of compound 7b

[0172] To compound 6b (1.90 g, 4.4 mmol), triethylamine (0.88 mL, 6.3 mmol) and 4-dimethyl-aminopyridine (53 mg, 0.4 mmol) in ice (0 °C) CH 2 Cl 2 To the solution (5 mL) was added isobutyryl chloride (0.55 mL, 5.2 mmol). After stirring at room temperature for 16 hours, the reactant was poured into EtOAc, and washed successively with 5% aqueous HCl, saturated NaHCO 3 , brine, and dry (Na 2 SO 4 ) and concentrated in vacuo to give compound 7b, which was used in the next step without any purification.

[0173] B) Preparation of Compound 8b

[0174] 70% HF / pyridine (2.0 mL) was added to a solution of crude compound 7b in THF (30 mL) in a polypropylene tube. After stirring at room temperature for 16 hours, triethylamine (2.0 mL) was add...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides 5'-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5'-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

Description

[0001] sequence listing [0002] A sequence listing in electronic format is submitted with this application. The provided sequence listing file is named CHEM0029WOSEQ.TXT, created on May 10, 2007, and has a size of 8kb. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety. technical field [0003] The present invention provides 5'-modified bicyclic nucleosides and oligomeric compounds and compositions prepared therefrom. More specifically, the present invention provides the formation of 2'-O-CH with other groups at the 5' position 2 -4' bridged nucleosides, and oligomers or compositions prepared therefrom. In a preferred embodiment, the 5'-group has a specific configuration that can form the (R) or (S) isomer. In some embodiments, the oligomeric compounds and compositions of the invention hybridize to a portion of a target RNA such that the target RNA is nonfunctional. Background technique [0004] Ant...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07H19/04C07H21/00
CPCC07H19/04C07H21/00A61P3/04A61P35/00
Inventor 普内特·P·塞思埃里克·E·斯威兹巴特·巴尔克利申
Owner IONIS PHARMA INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com